Recent epidemiological studies emphasize the importance of high density lipoproteins (HDL) as a protective factor against the development of atherosclerotic disease. It is likely that HDL exerts a beneficial effect on cholesterol homeostasis, probably involving an interaction between HDL and cell membranes. The proposed research aims to elucidate the structure and function of HDL, particularly the effect of cholesterol on HDL properties and HDL-mediated modifications of the composition of cell membranes. To determine their structure and thermodynamic properties, HDL apoproteins and their recombinants with HDL and egg yolk lecithins will be examined by differential scanning calorimetry, ultraviolet difference spectroscopy and negative stain electron microscopy. An attempt will be made to prepare discoid recombinants, resembling nascent HDL secreted by the liver and small intestine. Preliminary work shows that unesterified cholesterol has a profound effect on the formation and properties of HDL recombinants. The solubility of cholesterol in HDL discs and its effects on their structure and stability will be measured. The removal of cholesterol and phospholipid from cell membranes by HDL and its apoproteins will be studied, using the red blood cell membrane as a model. The relative effectiveness of different cholesterol acceptors will be determined, using several types of phospholipid presented to the membrane in different physical forms (e.g. as single walled vesicles, phospholipid/apoprotein discs or albumin/lecithin suspensions). These studies will help to understand the basic properties HDL and may give insight into potential physiological and pharmacological mechanisms for removal of cholesterol from normal and diseased tissues.